Synthesis, spectral studies and antimicrobial activity of 7-chloro-2-alkyl/aryl-4-alkyl/aryl- 3-arylidene-3H-1,5-benzodiazepines

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1 Indian Journal of hemistry Vol. 46B, July 2007, pp ote Synthesis, spectral studies and antimicrobial activity of 7-chloro-2-alkyl/aryl-4-alkyl/aryl- 3-arylidene-3H-1,5-benzodiazepines Vijai Pathak*, Rahul Joshi & eetu Gupta entre for Advanced Studies, Department of hemistry, University of Rajasthan, Jaipur , India Received 23 August 2006; accepted (revised) 9 March 2007 ondensation of various β-diketones 2 with appropriate araldehydes 1 in the presence of piperidene has afforded 2- arylidene-1,3-diketones 3 which in turn on condensation with 4- chloro-1,2-phenylene diamine in acidic medium give a series of 7- chloro-2-alkyl / aryl-4-alkyl / aryl-3-arylidene-3h-1,5-benzodiazepines 5a-j. All the newly synthesized compounds are characterized on the basis of their spectral (IR, 1 H MR, Mass) and analytical data. Representative compounds have been screened for their antibacterial and antifungal activities. Some of the compounds have been found to exhibit promising antibacterial and antifungal activities. Keywords: Antimicrobial, benzodiazepines, araldehydes, piperidene, β-diketones Since the discovery of flurazepam, flunitrazepam, quazepam, halazepam and triflubazam, the chemistry of benzodiazepines and allied compounds continues to draw attention of synthetic organic chemists due to their varied biological activities 1,2. A large number of benzodiazepine derivatives have been synthesized as sedative 3, tranquillizer 3, anticonvulsant 3, antidepressant 4, anxiolytic 4,5 and antihypertensive 6,7 drugs. Some benzodiazepines and allied derivatives are known to exhibit muscle relaxant 3, anticoagulant 8, antiobesity 9, antiulcer 10, calcium channel blocking 11, cholecystokinin antagonists 12, thrombopoietin receptor agonist 13, endothelin antagonist 14, vasopressin receptor antagonist 15,16 activity. From a structure activity stand point 2, generally electron withdrawing substituents at the 7-position of benzodiazepine moiety impart a high degree of activity and a rough rank order is: 2 F 3 > Br > l 3 F > H. It has been observed that introduction of l at 7- position of benzodiazepine moiety enhances the S activity greatly, for example, chlorodiazepoxide, oxazepam, quazepam and fletazepam are well known S drugs. Keeping these observations a comprehensive programme of developing some new halogenated benzodiazepine and allied derivatives have been undertaken and as a part of this the synthesis and antimicrobial activity of some 7-fluoroaryl-1H-1,4- diazepine 17, 3-arylazo-1H-1,5-benzodiazepine 18 and 6- arylazo-2,3-dihydro-1h-1,4-diazepines 19 have been already reported. ow in the present communication the synthesis, spectral studies and antimicrobial activity of 7-chloro- 2-alkyl /aryl-4-alkyl/aryl-3-arylidene-3h-1,5-benzodiazepines have been reported. Results and Discussion β-diketones 2 were prepared by condensation of different substituted acetophenones with appropriate ester according to the method of Joshi et al 20. β-diketones 2 were treated with appropriate araldehydes 1 in the presence of piperidine to give 2-arylidene-1,3-diketones 3. ondensation of 2-arylidene-1,3- diketones 3 with 4-chloro-1,2-phenylene diamine in the presence of gl. acetic acid afforded 7-chloro-2- alkyl/aryl-4-alkyl/aryl-3-arylidene-3h-1,5-benzodiazepines 5a-j. The reaction sequence is depicted in Scheme I. The synthesized compounds were characterized by IR, 1 H MR and mass spectral data. The IR spectra of 3a-j showed absorption bands in the region of (>= str.) and cm -1 (-=< str.). The IR spectra of 5a-j exhibited absorption band in the region of cm -1 (>= str.). The 1 H MR (Dl 3 ) spectra of compounds 5a-j exhibited resonance signal at δ ppm as multiplet for the aromatic protons and at ppm as singlet for the = proton. ompounds 5a-e showed singlet at δ ppm for the methyl protons. ompound 5d exhibited a resonance signal at δ 3.89 for the methoxy and = proton. Finally, the structure of compounds was confirmed by high resolution mass spectra. Mass spectra of compounds 5a-j showed molecular ion peak M. The mass fragmentation pathways of compound 5j are given in Scheme II. ompound 5j exhibited a molecular ion peak (M ) I at m/z corresponding to the molecular formula 23 H 15 lf 2 2 and M 1 peak

2 1192 IDIA J. EM., SE B, JULY R 1 H 2 R 2 2 Piperidine 3 R 1 R 2 3 H 2 H 2 4 l reflux ethanol Acetic acid R 1 R 2 5 l ompd R 1 R 2 ompd R 1 R 2 5a 4-l Me Me 5f 4-l Ph 4-l 6 H 4 5b 2-l Me Me 5g 4-F Ph 4-l 6 H 4 5c 2-3 Me Me 5h 4-l Me 4-l 6 H 4 5d 3,4,5-tri 3 Me Me 5i 4-F Me Ph 5e 3-F Me Me 5j 3,4-diF Me Ph at m/z due to isotopic carbon and hydrogen atoms. The molecular ion I further fragmented by two pathways A and B. In pathway-a, molecular ion I eliminated HF molecule to afford cation radical II at m/z (8.0%). The successive elimination of HF molecule and hydrogen radical from cation radical II gave a cation III at m/z (9.4 %) which in turn eliminated phenyl radical to afford cation radical IV at m/z (6.5%). ation radical IV extruded 2 moiety followed by scrambling of hydrogen to give cation radical V at m/z (18.9 %). In pathway-b, molecular ion I eliminated 2 HF 2 radical to give cation VI at m/z (20.2 %). The loss of 3 H radical from cation VI afforded cation radical VII at m/z (100.0 %) corresponding to the base peak, which was stabilized by resonance. The elimination of methyl radical from cation VI gave cation radical VIII at m/z (5.0%) which in turn lost a 7 H 2 moiety to give cation radical I at m/z (66.1 %). ation radical I eliminated 5 H 2 moiety to give cation at m/z (71.5 %). Antimicrobial activity Representative compounds were screened for their antibacterial activity against gram-negative bacteria Escherichia coli and gram-positive bacteria Scheme I Staphyllococcus aureus at 200, 400 and 800 ppm concentration. Antifungal activity was done against andida albicans and Aspergillus niger at 200, 400 and 800 ppm concentration. Streptomycin and Ketoconazole were used as standard drugs for antibacterial and antifungal evaluations, respectively. The compounds were screened for their biological activity by using inhibition zone technique 21. The results obtained for antibacterial and antifungal evaluations are recorded in Table I and Table II, respectively. The perusal of our results revealed that compounds possessing o-methoxy and m-fluoro substituents in the arylidene moiety of the synthesized compounds 5c, 5e, p-chloro, p-fluoro substituent in the arylidene moiety in combination with 4-chlorophenyl ring at 2-position of the synthesized compounds 5f, 5g and p-fluoro, 3,4-difluoro substituents in the arylidene moiety in combination with phenyl ring at 2-position of the synthesized compounds 5i, 5j showed higher degree of activity as compared to rest of the compounds against S.aureus at 200,400 and 800 ppm concentration. The compounds possessing o-methoxy and p-fluoro substituents in the arylidene moiety of the synthesized compounds 5c, 5i and p-chloro, p-fluoro substituent in the arylidene moiety in combination with p-chlorophenyl ring at 2-position of the synthesized

3 TES 1193 Path-A HF l 3 F F Path-B HF F l 3 F 23 H 15 lf 2 2 m/z (M ) I 3 l 3 23 H 14 lf 2 m/z II HF H l 21 H 14 l 2 m/z VI 3 H l 3 20 H 11 l 2 m/z VIII 7 H 2 l 3 l 23 H 12 l 2 m/z III 6 H H 7 l 2 m/z IV l l H 13 H 9 l 2 m/z I 5 H 2 H 3 8 H 7 l 2 m/z l 18 H 13 l 2 m/z VII (base peak) stabilized by resonance 3 2 l H l 3 16 H 5 l 2 m/z V Scheme II Mass fragmentation pattern of 7-chloro-2-phenyl-4-methyl-3-(3,4-difluorbenzylidene)-3H-1,5-benzodiazepine, 5j

4 1194 IDIA J. EM., SE B, JULY 2007 ompd Table I Antibacterial activity data of compounds 5a-j (800 ppm) IZ (AI) (400 ppm) IZ (AI) (200 ppm) IZ (AI) S. aureus E. coli S. aureus E. coli S. aureus E. coli Streptomycin a 8.0 (0.64) 9.5 (0.79) 6.0 (0.58) 7.0 (0.71) 4.5 (0.56) 4.1 (0.66) 5b 7.5 (0.60) 10.0 (0.83) 5.2 (0.50) 7.5 (0.76) 3.4 (0.42) 4.2 (0.68) 5c 15.0 (1.20) 12.5 (1.04) 12.0 (1.16) 10.2 (1.04) 9.0 (1.12) 6.4 (1.03) 5d 8.0 (0.64) 12.0 (1.0) 5.0 (0.48) 9.7 (0.99) 3.4 (0.42) 5.9 (0.95) 5e 13.0 (1.04) 8.0 (0.67) 10.6 (1.03) 5.1 (0.52) 8.2 (1.02) 3.0 (0.48) 5f 13.5 (1.08) 13.0 (1.08) 10.9 (1.06) 10.4 (1.06) 8.4 (1.05) 6.5 (1.04) 5g 14.0 (1.12) 13.2 (1.10) 11.0 (1.07) 10.4 (1.06) 8.3 (1.03) 6.5 (1.04) 5h 12.5 (1.0) 13.0 (1.08) 10.0 (0.97) 10.3 (1.05) 6.1 (0.76) 6.4 (1.03) 5i 13.0 (1.04) 14.0 (1.16) 10.7 (1.04) 11.0 (1.12) 8.2 (1.02) 6.6 (1.06) 5j 13.5 (1.08) 12.0 (1.0) 11.0 (1.07) 9.6 (0.98) 8.6 (1.07) 5.9 (0.95) IZ = Inhibition area (zone) excluding diameter of disc AI (Activity Index) = Inhibition area of sample/inhibition area of standard ompd Table II Antifungal activity data of compounds 5a-j (800 ppm) IZ (AI) (400 ppm) IZ (AI) (200 ppm) IZ (AI). albicans A. niger. albicans A. niger. albicans A. niger Ketoconazole a 12 (0.80) 9 (0.75) 9.2 (0.76) 6.7 (0.67) 7.3 (0.71) 4.2 (0.55) 5b 13.5 (0.90) 09 (0.75) 10.2 (0.84) 6.9 (0.69) 8.1 (0.79) 4.3 (0.56) 5c 15.0 (1.0) 15.5 (1.29) 12.0 (0.99) 12.0 (1.20) 10.1 (0.99) 8.9 (1.17) 5d 8.5 (0.57) 8.0 (0.67) 5.1 (0.42) 6.0 (0.60) 3.2 (0.31) 03 (0.39) 5e 15.5 (1.03) 12.0 (1.0) 12.3 (1.02) 10.0 (1.0) 10.3 (1.01) 7.5 (0.99) 5f 6.0 (0.40) 7.0 (0.58) 4.1 (0.34) 05 (0.50) 3.3 (0.32) 3.5 (0.46) 5g 7.0 (0.46) 9.2 (0.76) 5.4 (0.45) 7.0 (0.70) 3.8 (0.37) 4.1 (0.53) 5h 8.2 (0.54) 7.3 (0.61) 6.4 (0.53) 5.5 (0.55) 5.3 (0.51) 4.1 (0.53) 5i 10.5 (0.70) 11.0 (0.92) 6.8 (0.56) 8.9 (0.89) 5.1 (0.50) 6.2 (0.81) 5j 12.5 (0.83) 13.0 (1.08) 9.1 (0.75) 10.7 (1.07) 7.0 (0.69) 7.9 (1.04) IZ = Inhibition area (zone) excluding diameter of disc AI (Activity Index) = Inhibition area of sample/inhibition area of standard compound 5f, 5g, 5h showed higher degree of activity as compared to rest of the compounds against E.coli at 200, 400 and 800 ppm concentration. ompound possessing m-fluoro substituent in the arylidene moiety of the synthesized compound 5e showed higher degree of activity as compared to rest of the compounds against.albicans and the compounds possessing o- methoxy and 3,4-difluoro substituents in the arylidene moiety showed higher degree of activity against A.niger at 200, 400 and 800 ppm concentration. Experimental Section Melting points were determined in open glass capillary tubes and are uncorrected. The IR spectra (cm -1 ) were recorded on a Perkin-Elmer 557 grating infrared spectrophotometer in KBr pellets; 1 H MR spectra in Dl 3 (chemical shift in δ, ppm) on a Bruker spectrometer (200 MHz) using TMS as internal standard and mass spectra on a Esquire 3000 Bruker make spectrometer. The purity of the synthesized compounds was checked by TL on silica gel G in

5 TES 1195 various nonaqueous solvent systems. All the compounds gave satisfactory elemental analyses. Synthesis of 3-(4-chlorobenzylidene) pentane-2,4- dione 3a: A homogeneous mixture of 4-chlorobenzaldehyde (2.81 g, 20 mmoles), acetylacetone (2.0 g, 20 mmoles) and piperidine (0.02 ml) in chloroform (20 ml) was stirred at room temperature for about 50 hr. The mixture was diluted with chloroform and the piperidene was removed by washing with dilute hydrochloric acid followed by water. The chloroform layer was dried over MgS 4. The solvent was removed and the solid residue was recrystallized from ethanol. Molecular formula 12 H 11 l 2, yield 62%, m.p. 170 ; IR (KBr): 3055 (aromatic -H str.), 2830 (aliphatic -H str.), 1690 (>= str.), 1640 (>=< str.); 1 H MR (Dl 3 ): δ 2.90 (s, 6H, 3 ), 4.35 (s, 1H, ), (m, 4H, ArH). All other compounds 3b-j were prepared similarly. 3-(2-chlorobenzylidene) pentane-2,4-dione 3b: Mol. formula 12 H 11 l 2, yield 61%, m.p. 41 ; IR (KBr, cm -1 ): 3054 (aromatic -H str.), 2828 (aliphatic -H str.), 1690 (>= str.), 1640 (>= str.). 3-(2-Methoxybenzylidene) pentane-2,4-dione 3c: Mol. formula: 13 H 14 3, yield 65%, m.p. 98 ; IR (KBr, cm -1 ): 3055 (aromatic -H str.), 2835 (aliphatic -H str.), 1692 (>= str.), 1640 (>=< str.). 3-(3,4,5-Trimethoxybenzylidene) pentane-2,4-dione 3d: Mol. formula: 15 H 18 5, yield 60%, m.p. 85 ; IR (KBr, cm -1 ); 3050 (aromatic -H str.), 2845 (aliphatic -H str.), 1680 (>= str.), 1648 (>=< str.), 1238 (- str.). 3-(3-Fluorobenzylidene) pentane-2,4-dione 3e: Mol. formula: 12 H 11 F 2, yield 59%, m.p. 100 ; IR (KBr, cm -1 ): 3055 (aromatic -H str.), 2830 (aliphatic -H str,.), 1700 (>= str.), 1650 (>=< str.), 1265 (-F str.). 1-(4-hlorophenyl)-3-phenyl-2-(4-chlorobenzylidene) propane-1,3-dione 3f: Mol. formula: 22 H 14 l 2 2, yield 60%, m.p. 90, IR (KBr, cm -1 ); 3055 (aromatic -H str.), 1685 (>= str.), 1655 (>=< str.), 700 (-l str.). 1-(4-hlorophenyl)-3-phenyl-2-(4-fluorobenzylidene)propane-1,3-dione 3g: Molecular formula: 22 H 14 lf 2, yield 55%, m.p. 165, IR (KBr, cm -1 ): 3055 (aromatic -H str.), 1690 (>= str.), 1645 (>=< str.), 1270 (-F str.), 700 (-l str.). 1-(4-hlorophenyl)-2-(4-chlorobenzylidene) butane-1,3-dione 3h: Mol. formula: 17 H 12 l 2 2, yield 53%, m.p. 86, IR (KBr, cm -1 ): 3051 (aromatic -H str.), 2845 (aliphatic -H str.), 1685 (>= str.), 1650 (>=< str.), 727 (-l str.). 1-Phenyl-2-(4-fluorobenzylidene)butane-1,3-dione 3i: Mol. formula: 17 H 13 F 2, yield 64%, m.p. 96, IR (KBr, cm -1 ): 3055 (aromatic -H str.), 2830 (aliphatic -H str.), 1686 (>= str.), 1640 (>=< str.), 1275 (-F str.). 1-Phenyl-2-(3,4-difluorobenzylidene)butane-1,3- dione 3j: Mol. formula: 17 H 12 F 2 2, yield 61%, m.p. 88, IR (KBr, cm -1 ): 3060 (aromatic -H str.), 2830 (aliphatic -H str.), 1685 (>= str.), 1650 (>=< str.), 1275 (-F str.). 7-hloro-2,4-dimethyl-3-(4-chlorobenzylidene)- 3H-1,5-benzodiazepine 5a: A mixture of 4-chloro- 1,2-phenylene diamine (1.42 g, 10 mmoles), 3-(4- chlorobenzylidene) pentane-2,4-dione (2.22 g, 10 mmoles) and gl. acetic acid (1.0 ml) in ethanol (25 ml) was refluxed for 7 to 8 hr. The reaction mixture was cooled, hydrochloric acid (12, 10 ml) was added to it and the whole mixture was kept overnight at 0. The crystals of benzodiazepinium hydrochloride were filtered off, washed successively with cold ethanol, ether and dried. The crystals were recrystallized from ethanol. Treatment of 50% aqueous ethanolic solution of this hydrochloride with ammonia solution afforded the benzodiazepine free base. Mol. Formula: 18 H 14 l 2 2, Yield 45%, m.p. 140 ; IR (KBr): 3050 (aromatic -H str.), 2838 (aliphatic -H str.), 1651 (= str.), 1592 (>= str.), 1492 (aromatic = str.), 762 cm -1 (-l str.); 1 H MR (Dl 3 ): δ 2.83 (s, 6H, 3 ), 4.30 (s, 1H, ), (m, 7H, ArH); Mass (m/z) (%): M (11), (44.5), (100), (13.5), (82.3), (2.7); Anal. alcd for 18 H 14 l 2 2 (329):, 65.65; H, 4.25;, Found:, 65.55; H, 4.27;, 8.49%. All other compounds 5b-j were prepared by same procedure. 7-hloro-2,4-dimethyl-3-(2-chlorobenzylidene)- 3H-1,5-benzodiazepine 5b: Yield 48%, m.p. 172 ; IR (KBr): 3055 (aromatic -H str.), 2828 (aliphatic - H str.), 1640 (= str.), 1597 (>= str.), 1468 (aromatic = str.), 756 cm -1 (-l str.); 1 H MR (Dl 3 ): δ 2.82 (s, 6H, 3 ), 3.79 (s, 1H, ), (m, 7H, ArH); Mass (m/z) (%): M (13), (100), (44.4), (17.0), (16.3), (38.0), (12.8), (12.3); Anal. alcd for 18 H 14 l 2 2 (329):, 65.65; H, 4.25;, Found:, 65.54; H, 4.26;, 8.49%. 7-hloro-2,4-dimethyl-3-(2-methoxybenzylidene)- 3H-1,5-benzodiazepine 5c: Yield 47%, m.p. 176 ; IR (KBr): 3056 (aromatic -H str.), 2838 (aliphatic -H str), 1639 (= str.) 1597 (>= str.), 1463 (aromatic = str.), 1238 (- str.) 722 cm -1 (-l

6 1196 IDIA J. EM., SE B, JULY 2007 str.); Anal. alcd for 19 H 17 l 2 (324.5):, 70.26; H, 5.24;, Found:, 70.14; H, 5.23;, 8.61%. 7-hloro-2,4-dimethyl-3-(3,4,5-trimethoxybenzylidene)-3H-1,5-benzodiazepine 5d: Yield 49%, m.p. 160 ; IR (KBr): 3050 (aromatic -H str.), 2849 (aliphatic -H str.), 1639 (= str.), 1590 (>= str.), 1238 (- str.), 725 cm -1 (-l str.); 1 H MR (Dl 3 ): δ 2.35 (s, 6H, 3 ), 3.89 (s, 10H, 3 ), (m, 5H, ArH); Mass (m/z) (%): M (15), (9.5), (34.5), (20.2), (13.1), (100), (45.2), (19.0), (7.1), 63.4 (2.3); Anal. alcd for 21 H 21 l 2 3 (384.5):, 65.54; H, 5.46;, Found:, 65.44; H, 5.44;, 7.26%. 7-hloro-2,4-dimethyl-3-(3-fluorobenzylidene)- 3H-1,5-benzodiazepine 5e: Yield 46%, m.p. 145 ; IR (KBr): 3055 (aromatic -H str.), 2829 (aliphatic - H str.), 1638 (= str.), 1597 (>= str.), 1465 (aromatic = str.), 1270 (-F str.), 757 cm -1 (-l str.); 1 H MR (Dl 3 ): δ 2.40 (s, 6H, 3 ), 3.78 (s, 1H, ), (m, 7H, ArH); Mass (m/z) (%): M (15), (63.4), (28.3), (82.3), (100), (21.6), (24.3), (4.0); Anal. alcd for 18 H 14 lf 2 (312.5):, 69.12; H, 4.48;, Found:, 69.01; H, 4.49;, 8.94%. 7-hloro-2-(4-chlorophenyl)-4-phenyl-3-(4-chlorobenzylidene)-3H-1,5-benzodiazepine 5f: Yield 50%, m.p. 150 (d); IR (KBr): 3055 (aromatic -H str.), 1640 (= str.), 1593 (>= str.), 1490 (aromatic = str.), 700 cm -1 (-l str.); 1 H MR (Dl 3 ): δ 3.68 (s, 1H, ), (m, 16H, ArH); Anal. alcd for 28 H 17 l 3 2 (487.5):, 68.92; H, 3.49;, Found:, 68.80; H, 3.50;, 5.72 %. 7-hloro-2-(4-chlorophenyl)-4-phenyl-3-(4-fluorobenzylidene)-3H-1,5-benzodiazepine 5g: Yield 53%, m.p. 100 ; IR (KBr, cm -1 ): 3056 (aromatic -H str.), 1637 (= str.), 1595 (>= str.), 1480 (aromatic = str.), 1273 (-F str.), 703 (-l str.); 1 H MR (Dl 3 ): δ 3.60 (s, 1H, ), (m, 16H, ArH); Anal. alcd for 28 H 17 l 2 F 2 (471):, 71.34; H, 3.61;,, Found:, 71.20; H, 3.62;, 5.93%. 7-hloro-2-(4-chlorophenyl)-4-methyl-3-(4-chlorobenzylidene)-3H-1,5-benzodiazepine 5h: Yield 49%, m.p. 156 ; IR (KBr, cm -1 ): 3055 (aromatic -H str.), 2849 (aliphatic -H str.), 1655 (= str.), 1589 (>= str.), 1490 (aromatic = str.), 727 (-l str.); 1 H MR (Dl 3 ): δ 2.80 (s, 3H, 3 ), 3.61 (s, 1H, ), (m, 11H, ArH); Mass (m/z) (%): M (20%), (4.0), (8.1), (8.1), (42.1), (55.7), (46.2), (100), (4), (80), (2.7); Anal. alcd for 23 H 15 l 3 2 (425.5):, 64.86; H, 3.52;, Found:, 64.71; H, 3.53;, 6.57%. 7-hloro-2-phenyl-4-methyl-3-(4-fluorobenzylidene)-3H-1,5-benzodiazepine 5i: Yield 53%, m.p. 79 ; IR (KBr, cm -1 ): 3055 (aromatic -H str.), 2828 (aliphatic -H str.), 1639 (= str.), 1590 (>= str.), 1473 (aromatic = str.), 1275 (-F str.), 721 (-l str.); 1 H MR (Dl 3 ): δ 2.82 (s, 3H, 3 ), 3.80 (s, 1H, ), (m, 12H, ArH); Anal. alcd for 23 H 16 lf 2 (374.5):, 73.70; H, 4.27;, Found:, 73.58; H, 4.29;, 7.47%. 7-hloro-2-phenyl-4-methyl-3-(3,4-difluorobenzylidene)-3H-1,5-benzodiazepine 5j: Yield 54%, m.p. 96 (d); IR (KBr, cm -1 ): 3061 (aromatic -H str.), 2830 (aliphatic -H str.), 1657 (= str.), 1600 (>= str.), 1448 (aromatic = str.), 1275 (-F str.), 765 (-l str.); 1 H MR (Dl 3 ): δ 2.85 (s, 3H, 3 ), 3.91 (s, 1H, ), (m, 11H, ArH); Mass (m/z) (%): M (21%), (8.0%), (9.4), (20.2), (5.0%), (100), (6.5%), (18.9), (66.1), (71.5); Anal. alcd for 23 H 15 lf 2 2 (392.5):, 70.32; H, 3.82;, Found, 70.21; H, 3.82;, 7.11%. Acknowledgements Authors are thankful to UG for financial assistance and to Dr S M Jain, Joint Director, RRL Jammu for providing spectral data, Dr Anita Singhal, SMS Medical ollege for help offered in antimicrobial activity, and SIR, ew Delhi for award of Senior Research Fellowship to one of us (G). References 1 Kelly T A & Patel U R, J rg hem, 60(6), 1995, Elliott A J, The Role of Fluorine in the Development of entral ervous System Agents in Biomedicinal Aspects of Fluorine hemistry, Filler R & Kobayashi Y, (Elsevier Biomedicinal press, Amsterdam, ew York, xford, 1982 Edn. 3 Hara T, Shikayama Y, Ito K, Mori T, Fujimori H, Sunami T, Hashimoto Y & Ishimoto Y, Jpn Tokkyo Koho Jp 61 01, 433, 1986; hem Abstr, 104, 1986, a. 4 Ishikawa & Takaoka A, Jpn Kokai Tokkyo Koho JP 62, 178, 574, 1988; hem Abstr, 108, 1988, 75435c. 5 Scott M K, Demeter D A, ortey S, Dubinsky B, Shank R P & Reitz A B, Prog Med hem, 36, 1999, Atwal K, US 4, 650, 797, 1987; hem Abstr, 107, 1987, 77843n. 7 Atwal K S, Eur Pat App EP 211, 429, 1987; hem Abstr, 107, 1987, a. 8 Hirayama F, Koshio H, Ishihara T, Kaizawa H, Katayama, Taniuchi Y & Matsumoto Y, PT Int App, W 99 37, 643, 1999; hem Abstr, 131, 1999, q. 9 olclough D, Hodgson A & Szewczyk J R, PT Int App W 00 68, 209, 2000; hem Abstr, 133, 2000, c.

7 TES Hagishita Y, Seno K, Myakoshi M, Tsushima T & Ishihara Y, Jpn Kokai Tokkyo Koho JP 07 97, 371, 1995; hem Abstr, 123, 1995, t. 11 Atwal K S, Bergey J L, Hedberg A & Moreland S, J Med hem, 30(4), 1987, Bock M G, DiPardo R M, Evans B E, Rittle K E, Freidinger R M, hang R S L & Lotti V J, J Med hem, 31(1), 1988, Watanabe Y, Kimura T, Kaburagi H, Iwasaki & Ikeda Y, Jpn Kokai Tokkyo Koho JP 11152, 276, 1999; hem Abstr, 131, 1999, 44853h. 14 Murugesan, US 5, 420, 123, 1995; hem Abstr, 123, 1995, d. 15 Steffan R J & Failli A A, PT Int App W 00 46, 228, 2000; hem Abstr, 133, 2000, a. 16 Hoekstra W J, Dyatkin A B, Maryanoff B E & Matthews J M, PT Int App W 0043, 398, 2000; hem Abstr, 133, 2000, a. 17 Pathak V, Joshi R, Tiwari R & Gupta, Indian J Heterocycl hem, 11, 2002, Pathak V, Joshi R, Gupta & Rao V M, Indian J Heterocycl hem, 12, 2003, Pathak V, Joshi R & Gupta, Indian J Heterocycl hem, 14, 2005, Joshi K, Pathak V & Bhargava S, J Inorg ucl hem, 39, 1977, Bryant M, Antibiotics and Their Laboratory ontrol (Butterworth, London, 1968, 26.